Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
Project description:Cigarette smoke is associated with the majority of lung cancers: however, 25% of lung cancer patients are non-smokers, and half of all newly diagnosed lung cancer patients are former smokers. Lung tumors exhibit distinct epidemiological, clinical, pathological, and molecular features depending on smoking status, suggesting divergent mechanisms underlie tumorigenesis in smokers and non-smokers. MicroRNAs (miRNAs) are integral contributors to tumorigenesis and mediate biological responses to smoking. Based on the hypothesis that smoking-specific miRNA differences in lung adenocarcinomas reflect distinct tumorigenic processes selected by different smoking and non-smoking environments, we investigated the contribution of miRNA disruption to lung tumor biology and patient outcome in the context of smoking status. Results: We discovered novel and distinct smoking-status-specific patterns of miRNA and miRNA-mediated gene networks, and identified miRNAs that were prognostically significant in a smoking-dependent manner. Conclusions: We conclude that miRNAs disrupted in a smoking-status-dependent manner affect distinct cellular pathways and differentially influence lung cancer patient prognosis in current, former and never smokers. Our findings may represent promising biologically relevant markers for lung cancer prognosis or therapeutic intervention. We applied a whole transcriptome sequencing based approach to interrogate miRNA levels in 94 patient-matched lung adenocarcinoma and non-malignant lung parenchymal tissue pairs from current [CS], former [FS] and never smokers [NS].
Project description:Although smoking is the major risk factor for lung cancer, only 7% of female lung cancer patients in Taiwan have a history of cigarette smoking, extremely lower than those in Caucasian females. This report is a comprehensive analysis of the molecular signature of non-smoking female lung cancer in Taiwan.
Project description:Prior microarray studies of smokers at high risk for lung cancer have demonstrated that heterogeneity in bronchial airway epithelial cell gene expression response to smoking can serve as an early diagnostic biomarker for lung cancer. This study examines the relationship between gene expression variation and genetic variation in a central molecular pathway (NRF2-mediated antioxidant response) associated with smoking exposure and lung cancer. We assessed global gene expression in histologically normal airway epithelial cells obtained at bronchoscopy from smokers who developed lung cancer (SC, n=20), smokers without lung cancer (SNC, n=24), and never smokers (NS, n=8). Functional enrichment showed that the NRF2-mediated antioxidant response pathway differed significantly among these groups. Keywords: Global mRNA expression profiling 21 total arrays (20 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers with Lung Cancer 30 total arrays (24 unique patients) run on total RNA obtained from Bronchial Epithelium of Smokers without Lung Cancer 9 total arrays (8 unique patients) run on total RNA obtained from Bronchial Epithelium of Never Smokers
Project description:East-Asian (EA) patients with Non Small Cell Lung Cancer (NSCLC) are associated with a high proportion of non-smoking women, EGFR activating somatic mutations, and clinical responses to tyrosine kinase inhibitors. We identify copy number alterations specific to EA and Western European (WE) NSCLCs and conducted an integrative analysis using transcritomic data for identifying copy-number-driven candidate genes. Samples were hybridized to Affymetrix Genome-Wide Human SNP 6.0 arrays according to the manufacturer’s specifications in the same center. 226 lung adenocarcinomas (90 East-Asian and 136 Western-European) were analyzed for copy-number aberrations (CNAs) using a common high resolution SNP microarray platform.